Synergistic effect of Linebacker-1 (LB1) with radiotherapy in a mouse lung cancer model

ABSTRACTPurpose Myricetin is a small molecular weight FDA-recognized dietary supplement showing efficient anticancer effects. The recent development of myricetin derivative Linebacker-1 (LB1), which changes a hydroxyl group on the B-ring to a chlorine atom, exhibits DNA-binding ability by interacting with the minor grooves of DNA and may also act as an anti-tumor drug. This study demonstrates the anticancer effect and radio-sensitization of LB1 in a lung cancer model. Methods In vitro studies were performed in human A549 (ATCC) and HT29 (ATCC) and in murine LLC1 (ATCC) cancer cell lines. A syngeneic murine model of lung adenocarcinoma was generated subcutaneously in one flank of wild (+/+) C57/BL6 background mice using the LLC1 cell line. Image-guided radiotherapy (IGRT) targeting the tumor was administered with a small animal radiation research platform (SARRP). Results Our in vitro study observations demonstrate that LB1 induces an antineoplastic effect in human lung A549 (pConclusion LB1 demonstrates enhancement of the anti-tumor effect of radiation in a lung cancer model, while antiPD1 treatment further enhances the effect. The results provide impetus for further studies, including in vivo studies in orthotopic lung cancer models, to provide robust pre-clinical data for potential future application of LB1 as a radio-sensitizer in the clinic.